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Study of isoniazid-resistant tuberculosis: mycobacterial genotypic characterization and clinical features in human subjects

STUDY OF ISONIAZID-RESISTANT TUBERCULOSIS: MYCOBACTERIAL
GENOTYPIC CHARACTERIZATION AND CLINICAL FEATURES IN HUMAN
SUBJECTS
by
Patricio Escalante
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(CLINICAL AND BIOMEDICAL INVESTIGATIONS)
August 2007
Copyright 2007 Patricio Escalante

Most isoniazid-resistant (INHr) M. tuberculosis (MTB) isolates have katG mutations. KatG is a virulence factor in animal models. We aim to determine if MTB-INHr genotype is associated with distinct clinical features. A retrospective case-control study design was used to compare clinical characteristics of patients infected with INHr-MTB (katG or non-katG mutations) to patients with pan-sensitive (PS) MTB isolates. Univariate and multivariate analyses were used. Twenty-nine INHr-TB cases and 50 PS controls were evaluated. INHr-MTB patients infected with non-katG mutants were associated with a higher rate of sputum conversion at 1 month of treatment: Adjusted OR = 6.03 (95%CI: 1.02-35.4; P = 0.04). Patients infected with katG mutants were associated with a higher rate of unilateral lung disease: Adjusted OR = 10.7 (95%CI: 1.1-107; P = 0.04). Some MTB mutations resulting in INH resistance may be associated with a faster response to treatment, and others with a more contained pulmonary involvement.

STUDY OF ISONIAZID-RESISTANT TUBERCULOSIS: MYCOBACTERIAL
GENOTYPIC CHARACTERIZATION AND CLINICAL FEATURES IN HUMAN
SUBJECTS
by
Patricio Escalante
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(CLINICAL AND BIOMEDICAL INVESTIGATIONS)
August 2007
Copyright 2007 Patricio Escalante